Diphtheria toxin and related proteins: effect of route of injection on toxicity and the determination of cytotoxicity for various cultured cells.
The effect of route of injection on the toxicity of intact diphtheria toxin, cross-reacting material (CRM45), and diphtherial fragment A was compared in several animal species. By ordinary routes of injection, neither CRM45 nor fragment A was toxic, even in species for which 0.1 micrograms of toxin/kg of body weight was lethal. After intracerebral injection, however, small amounts of CRM45 led to paralysis and death, even in mice and rats--species that are resistant to toxin administered intravenously. High doses of fragment A were nontoxic even by the intracerebral route. The cytotoxic dose od CRM45 was approximately 10(-7) M for a variety of cell lines derived from toxin-sensitive or toxin-resistant species. Cultured at Schwann's cells, however, were more sensitive CRM45 than other cell lines tested and 50-100 times more sensitive to toxin than cells cultured from other adult rat tissues. Fragment A has virtually no cytotoxicity for any mammalian cell line tested.
D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D012831:Bombyx; D002478:Cells, Cultured; D002645:Chickens; D002522:Chlorocebus aethiops; D003353:Corynebacterium diphtheriae / Q000276:immunology; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D004306:Dose-Response Relationship, Immunologic; D006168:Guinea Pigs; D006801:Humans; D007928:Lethal Dose 50; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000276:immunology
D001426:Bacterial Proteins; C033445:CRM45 fragment of diphtheria toxin; D004167:Diphtheria Toxin; D010446:Peptide Fragments; D011971:Receptors, Immunologic; C029795:diphtheria toxin fragment A; C028581:CRM197 (non-toxic variant of diphtheria toxin)